TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

J Control Release. 2016 Feb 10;223:215-223. doi: 10.1016/j.jconrel.2015.12.048. Epub 2015 Dec 28.

Abstract

Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.

Keywords: Circulating tumor cells; Metastasis; Nanomedicine; TRAIL.

MeSH terms

  • Animals
  • E-Selectin / administration & dosage*
  • E-Selectin / therapeutic use
  • Humans
  • Leukocytes* / metabolism
  • Liposomes
  • Male
  • Mice, Transgenic
  • Neoplasm Metastasis / prevention & control
  • Neoplastic Cells, Circulating / drug effects*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage*
  • TNF-Related Apoptosis-Inducing Ligand / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • E-Selectin
  • Liposomes
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human